Hipoksija u regulaciji upale i rasta tumora

undergraduate thesis

• Title (english): Hypoxia in regulation of inflammation and tumor growth
• Author: Marko Marohnić
• Mentor: Nada Oršolić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-09-15, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Nedostatak kisika, tj. hipoksija, značajan je čimbenik tumorskog mikrookoliša koji promovira rast, razvoj i napredak tumora posredno preko HIF-1 transkripcijskog čimbenika. HIF-1 je značajan u poticanju angiogeneze ekspresijom gena za određene angiogene čimbenike, poput VEGF-a koji potiče grananje i stvaranje novih ogranaka krvnih žila. HIF-1 ima ulogu u poticanju metastaziranja koje tumoru omogućava invaziju u udaljena tkiva i na taj način njegov daljnji napredak. Kako bi tumorske stanice dobivale dovoljno energije za rast i dijeljenje uslijed nedostatka terminalnog akceptora elektrona nužna je promjena metaboličkog puta oksidativne fosforilacije na glikolitički put u procesu koji se naziva Warburg efekt, a potiče ga HIF-1. Određeni čimbenici upalnih procesa djeluju u suradnji s HIF-1 čimbenikom kako bi osigurali rast i razvoj tumora. Pomoću nekoliko mehanizama tumorske stanice posredno preko HIF-1 čimbenika izbjegavaju i suzbijaju imunosni odgovor i potiču imunosupresiju kako stanice imunosnog sustava ne bi obustavile njihov daljnji rast i širenje. Različite imunosupresivne molekule, ali i sam mikrookoliš tumora reguliraju funkciju stanica imunosnog sustava. Uz povišene koncentracije laktata i H+ iona, koji su direktna posljedica izmjenjenog metabolizma tumora, adenozin, VEGF i pozicioniranje fosfatidilserina na vanjskoj strani stanične membrane potiču imunosupresiju.

Abstract (english)

Lack of oxygen (hypoxia) is an important factor in tumor microenviroment (TME) that promotes HIF-1 mediated growth and progression of tumors. HIF-1 factor's role is significant in inducing angiogenesis by expressing genes for angiogenic factors active in this process, such as VEGF which promotes branching and generation of new blood vessels. HIF-1 also has a role in inducing metastasis, a process that enables tumor invasion in distant tissues and promotes their further progression. In order for tumor cells to obtain enough energy for proliferation and growth while the terminal electron acceptor is absent, tumor cells undergo a metabolic switch from oxidative phosphorylation to glycolysis in a process called the Warburg effect induced by HIF-1. Certain inflammation factors cooperate with HIF-1 in order to ensure tumor growth and development. HIF-1 mediates a number of mechanisms that are used by tumor cells to evade immune response and promote imunosupression in order to stop immune cells from inhibiting tumor growth and spread. Various immunosupressive molecules and TME regulate immune cell function. High lactate and H+ ion concentrations (which is a direct result of a tumor cell metabolic switch to glycolysis via Warburg effect) together with adenosine, VEGF and phosphatidylserine positioning on outer membrane leaflet promote imunosupression.

• Keywords: hipoksija; tumori
• Language: croatian
• URN:NBN: urn:nbn:hr:217:443027
• Study programme: Title: Ecology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-09-23 12:40:17